InterPro domain: IPR032106

This domain is found at the N terminus of 2-oxoglutarate dehydrogenase component E1 [ 1 ].

2-oxoglutarate dehydrogenase is a key enzyme in the TCA cycle, converting 2-oxoglutarate, coenzyme A and NAD(+) to succinyl-CoA, NADH and carbon dioxide [ 2 ]. This activity of this enzyme is tightly regulated and it is a major determinant of the metabolic flux through the TCA cycle. This enzyme is composed of multiple copies of three different subunits: 2-oxoglutarate dehydrogenase (E1), dihydrolipoamide succinyltransferase (E2) and lipoamide dehydrogenase (E3) which is often shared with similar enzymes such as pyruvate dehydrogenase [ 3 ]. The E2 component forms a large multimeric core which binds the peripheral E1 and E3 subunits. The substrate is transferred between the active sites of the different subunits by a lipoyl moiety, bound to a lysine residue from the E2 polypeptide.

1. Sequences directing dihydrolipoamide dehydrogenase (E3) binding are located on the 2-oxoglutarate dehydrogenase (E1) component of the mammalian 2-oxoglutarate dehydrogenase multienzyme complex. EMBO J. 11, 3229-35
2. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Philos. Trans. R. Soc. Lond., B, Biol. Sci. 360, 2335-45
3. 2-Oxo acid dehydrogenase multienzyme complexes. The central role of the lipoyl domain. Biol. Chem. 378, 617-34